This proposal will build on the successful efforts from Phase I, which served to characterize the technology's accuracy and limits of detection and provide proof of concept data on mucosal biopsy samples from patients with colorectal cancer. We aim to (1) Develop a prototype analytical system incorporating Enumeral's technology, including automation, software and data analysis and (2)Test prototypes on clinical samples in collaborating academic laboratories to demonstrate clinical utility and advantages over analytical current techniques. Our collaborators include Jedd Wolchok (Memorial Sloan Kettering Cancer Center), who led clinical efforts for breakthrough cancer immunotherapies ipilimumab and nivolumab, Douglas Kwon (Ragon Institute), whose lab has expertise in mucosal immunology and extensive experience with Enumeral's technology; Elizabeth Hillman (Columbia University), who has expertise in developing novel optical imaging systems; Jason Ruan (VigeneTech) who is an expert in image analysis and software development, and Paul and Doug Sabin (Fikst) who are experts in produce development. The use of Enumeral's platform to understand cellular function and responses to therapy in resident tissues can potentially have a significant impact on early cancer diagnosis, understanding mechanisms of disease progression, and, ultimately development of novel, effective, and safe immunotherapies.